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Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo

  • Authors:
    • Huaqi Zhu
    • Qiman Sun
    • Changjun Tan
    • Min Xu
    • Zhi Dai
    • Zheng Wang
    • Jia Fan
    • Jian Zhou
  • View Affiliations / Copyright

    Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 585-592
    |
    Published online on: June 5, 2014
       https://doi.org/10.3892/mmr.2014.2302
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Abstract

The aim of our study was to elucidate the effect of tacrolimus (FK506) and of C-X-C chemokine receptor type 4 (CXCR4), which is a receptor specific to the stromal cell-derived factor-1α (SDF‑1α), on growth and metastasis of hepatocellular carcinoma (HCC). Following treatment with different concentrations of FK506, AMD3100 or normal saline (NS), the proliferation of Morris rat hepatoma 3924A (MH3924A) cells was measured by the MTT assay, the expression of CXCR4 was analyzed with immunohistochemistry, and the morphological changes and the invasiveness of cells were studied with a transwell assay and under a scanning electron microscope, respectively. In addition, August Copenhagen Irish rat models implanted with tumor were used to examine the pathological changes and invasiveness of tumor in vivo, the expression of CXCR4 in tumor tissues and the expression of SDF‑1α in the adjacent tissues to the HCC ones, using immunohistochemistry. In vitro, FK506 (100‑1,000 µg/l) significantly promoted the proliferation of MH3924A cells (P<0.01), and increased the expression of CXCR4 in MH3924A cells, albeit with no significance (P>0.05). By contrast, AMD3100 had no effect on the proliferation of MH3924A cells, but significantly reduced the expression of CXCR4 (P<0.05). The invasiveness of MH3924A cells was significantly (P<0.01) enhanced following treatment with FK506, SDF‑1α, FK506 + AMD3100, FK506 + SDF‑1α or FK506 + AMD3100 + SDF‑1α. In vivo, tumor weight (P=0.041), lymph node metastasis (P=0.002), the number of pulmonary nodules (P=0.012), the expression of CXCR4 in tumor tissues (P=0.048) and that of SDF‑1α in adjacent tissues (P=0.026) were significantly different between the FK506-treated and the NS group. Our results suggest that FK506 promotes the proliferation of MH3924A cells and the expression of CXCR4 and SDF‑1α in vivo. Therefore, inhibiting the formation of the CXCR4/SDF‑1α complex may partly reduce the promoting effect of FK506 on HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu H, Sun Q, Tan C, Xu M, Dai Z, Wang Z, Fan J and Zhou J: Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo. Mol Med Rep 10: 585-592, 2014.
APA
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z. ... Zhou, J. (2014). Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo. Molecular Medicine Reports, 10, 585-592. https://doi.org/10.3892/mmr.2014.2302
MLA
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z., Fan, J., Zhou, J."Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo". Molecular Medicine Reports 10.2 (2014): 585-592.
Chicago
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z., Fan, J., Zhou, J."Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo". Molecular Medicine Reports 10, no. 2 (2014): 585-592. https://doi.org/10.3892/mmr.2014.2302
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu H, Sun Q, Tan C, Xu M, Dai Z, Wang Z, Fan J and Zhou J: Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo. Mol Med Rep 10: 585-592, 2014.
APA
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z. ... Zhou, J. (2014). Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo. Molecular Medicine Reports, 10, 585-592. https://doi.org/10.3892/mmr.2014.2302
MLA
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z., Fan, J., Zhou, J."Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo". Molecular Medicine Reports 10.2 (2014): 585-592.
Chicago
Zhu, H., Sun, Q., Tan, C., Xu, M., Dai, Z., Wang, Z., Fan, J., Zhou, J."Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF‑1α expression in vivo". Molecular Medicine Reports 10, no. 2 (2014): 585-592. https://doi.org/10.3892/mmr.2014.2302
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